PRODUCT MONOGRAPH
HEPARIN SODIUM and 0.9% SODIUM CHLORIDE INJECTION
Heparin Sodium
Intravenous solution
1000 USP Heparin Units in 500mL 0.9% Sodium Chloride Injection
2000 USP Heparin Units in 1000mL 0.9% Sodium Chloride Injection
Anticoagulant
Baxter Corporation
7125 Mississauga Road
Mississauga
Ontario
Canada L5N 0C2
Date of Preparation:
July 05, 2013
Submission Control No: 162990
Product Monograph - Heparin Sodium and 0.9% Sodium Chloride
Page 1 of 17
Table of Contents
PART I: HEALTH PROFESSIONAL INFORMATION ........................................................ 3
SUMMARY PRODUCT INFORMATION........................................................................ 3
INDICATIONS AND CLINICAL USE ............................................................................. 3
CONTRAINDICATIONS ................................................................................................... 3
WARNINGS AND PRECAUTIONS ................................................................................. 3
ADVERSE REACTIONS ................................................................................................... 7
DOSAGE AND ADMINISTRATION ............................................................................... 9
OVERDOSAGE ................................................................................................................ 10
ACTION AND CLINICAL PHARMACOLOGY ............................................................ 10
STORAGE AND STABILITY ......................................................................................... 11
SPECIAL HANDLING INSTRUCTIONS ....................................................................... 11
DOSAGE FORMS, COMPOSITION AND PACKAGING............................................. 11
PART II: SCIENTIFIC INFORMATION .............................................................................. 13
PHARMACEUTICAL INFORMATION ......................................................................... 13
TOXICOLOGY ................................................................................................................. 14
PART III: CONSUMER INFORMATION ............................................................................. 15
Product Monograph - Heparin Sodium and 0.9% Sodium Chloride
Page 2 of 17
HEPARIN SODIUM AND 0.9% SODIUM CHLORIDE INJECTION
Heparin Sodium
PART I: HEALTH PROFESSIONAL INFORMATION
SUMMARY PRODUCT INFORMATION
Route of
Administration
Intravenous
Dosage Form /
Strength
Clinically Relevant Nonmedicinal
Ingredients
Citric Acid,Anhydrous, USP
Solution/
Dibasic Sodium Phosphate, USP
2 unit/ml of Heparin
Sodium and 9mg/ml of For a complete listing see Dosage Forms,
Composition and Packaging section.
Sodium Chloride
INDICATIONS AND CLINICAL USE
Heparin Sodium in 0.9% Sodium Chloride Injection (Heparin Sodium, USP and Sodium Chloride, USP) is
indicated for anticoagulant therapy:
• in extracorporeal circulation,
• in dialysis procedures,
• as an aid in the maintenance of catheter patency.
CONTRAINDICATIONS
Heparin sodium is contraindicated in patients:
• with uncontrollable bleeding (see WARNINGS AND PRECAUTIONS), except when this is due to
disseminated intravascular coagulation.
• with a known hypersensitivity to heparin sodium or porcine derivatives or to any ingredient in the formulation
or component of the container (for a complete listing, see DOSAGE FORMS, COMPOSITION AND
PACKAGING).
• with severe thrombocytopenia.
• when suitable blood coagulation tests cannot be performed at appropriate intervals (for full-dose heparin sodium
therapy). There is usually no need to monitor the effect of low-dose heparin in patients with normal coagulation
parameters.
WARNINGS AND PRECAUTIONS
Product Monograph - Heparin Sodium and 0.9% Sodium Chloride
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Heparin is not intended for intramuscular use.
Do not use Heparin Sodium in 0.9% Sodium Chloride Injection as a “catheter lock flush” product. Heparin Sodium
in 0.9% Sodium Chloride Injection is not suitable for this use. Use only products approved for catheter lock to
perform catheter lock flush procedures.
Carefully examine all presentations of heparin sodium to confirm the correct formulation prior to administration of
the drug.
Allergic reactions
There is experimental evidence that heparin may modify or inhibit allergic reactions. However, the application of
these findings to human patients has not been fully defined.
Hypersensitivity reactions have been reported with chills, fever and urticaria as the most usual manifestations.
Asthma, rhinitis, lacrimation, and anaphylactoid reactions have also been reported.
Vasospastic reactions may develop independent of the origin of heparin, 6 to 10 days after the initiation of the
therapy and last for 4 to 6 hours. The affected limb is painful, ischemic and cyanosed. An artery to this limb may
have been recently catheterized. After repeat injections, the reaction may gradually increase to include generalized
vasospasm, with cyanosis, tachypnea, feeling of oppression and headache.
Hemorrhage
Heparin Sodium should be used with extreme caution in disease states in which there is increased danger of
hemorrhage.
Heparin sodium should be used with extreme care in patients suffering from conditions in which there is increased
danger of hemorrhage, for example:
Cardiovascular
Subacute bacterial endocarditis, arteriosclerosis, severe hypertension, increased capillary permeability
during and immediately following:
a. spinal tap or spinal anesthesia.
b. major surgery, especially involving the brain, spinal cord, or eye.
Hematologic
Conditions associated with increased bleeding tendencies such as hemophilia, some purpuras and
thrombocytopenia.
Gastrointestinal
Conditions associated with inaccessible ulcerative lesions and continuous tube drainage of stomach or small
intestine.
Other
Menstruation, liver disease with impaired hemostasis.
Adrenal hemorrhage with resultant acute adrenal insufficiency has occurred during anticoagulant therapy.
Therefore, such treatment should be discontinued in patients who develop signs and symptoms compatible with
acute adrenal hemorrhage and insufficiency. Plasma cortisol levels should be measured immediately, and vigorous
therapy with intravenous corticosteroids should be instituted promptly. Initiation of therapy should not depend
Product Monograph - Heparin Sodium and 0.9% Sodium Chloride
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upon laboratory confirmation of the diagnosis, since any delay in an acute situation may result in the patient’s
death.
Coagulation testing
Administration of Heparin Sodium when used in therapeutic dosage should be regulated by frequent blood
coagulation tests. If the coagulation tests are unduly prolonged or if hemorrhage occurs, Heparin Sodium should be
promptly discontinued (See OVERDOSAGE).
Thrombocytopenia
Thrombocytopenia has been reported to occur in patients receiving heparin with a reported incidence of up to 30%.
Platelet counts should be obtained at baseline and periodically during heparin administration. Mild
thrombocytopenia (count greater than 100,000/mm3) may remain stable or reverse even if heparin is continued.
However, thrombocytopenia of any degree should be monitored closely. If the count falls below 100,000/mm3 or if
recurrent thrombosis develops (see Heparin-induced Thrombocytopenia (HIT) With or Without Thrombosis),
the heparin product should be discontinued and, if necessary, an alternative anticoagulant administered.
Heparin-induced Thrombocytopenia (HIT) (With or Without Thrombosis)
HIT is a serious immune-mediated reaction resulting from irreversible aggregation of platelets. HIT may progress to
the development of venous and arterial thromboses, a condition referred to as HIT with thrombosis. Thrombotic
events may also be the initial presentation for HIT. These serious thromboembolic events include deep vein
thrombosis, pulmonary embolism, cerebral vein thrombosis, limb ischemia, stroke, myocardial infarction,
mesenteric thrombosis, renal arterial thrombosis, skin necrosis, gangrene of the extremities that may lead to
amputation, and fatal outcomes.
Once HIT (with or without thrombosis) is diagnosed or strongly suspected, all heparin sodium sources (including
heparin flushes) should be discontinued and an alternative anticoagulant used. Future use of heparin sodium,
especially within 3 to 6 months following the diagnosis of HIT (with or without thrombosis), and while patients test
positive for HIT antibodies, should be avoided.
Immune-mediated HIT is diagnosed based on clinical findings supplemented by laboratory tests confirming the
presence of antibodies to heparin sodium, or platelet activation induced by heparin sodium. A drop in platelet count
greater than 50% from baseline is considered indicative of HIT. Platelet counts begin to fall 5 to 10 days after
exposure to heparin sodium in heparin sodium–naïve individuals, and reach a threshold by days 7 to 14. In contrast,
“rapid onset” HIT can occur very quickly (within 24 hours following heparin sodium initiation), especially in
patients with a recent exposure to heparin sodium (i.e. previous 3 months). Thrombosis development shortly after
documenting thrombocytopenia is a characteristic finding in almost half of all patients with HIT.
Thrombocytopenia of any degree should be monitored closely. If the platelet count falls below 100,000/mm3 or if
recurrent thrombosis develops, the heparin product should be promptly discontinued and alternative anticoagulants
considered if patients require continued anticoagulation.
Delayed Onset of HIT (With or Without Thrombosis)
Heparin-induced thrombocytopenia (with or without thrombosis) can occur up to several weeks after the
discontinuation of heparin therapy. Patients presenting with thrombocytopenia or thrombosis after discontinuation
of heparin sodium should be evaluated for HIT (with or without thrombosis).
Product Monograph - Heparin Sodium and 0.9% Sodium Chloride
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Fluid overload
The intravenous administration of these solutions can cause fluid and/or solute overloading resulting in dilution of
serum electrolyte concentrations, overhydration, congested states, or pulmonary edema. The risk of dilutional states
is inversely proportional to the electrolyte concentrations of the solutions. The risk of solute overload causing
congested states with peripheral and pulmonary edema is directly proportional to the electrolyte concentrations of
the solutions.
General
Do not administer unless the solution is clear.
Reactions which may occur because of the solution or the technique of administration of Heparin Sodium in 0.9%
Sodium Chloride Injection include: febrile response; infection at the site of injection; venous thrombosis or
phlebitis extending from the site of injection; extravasation; and hypervolemia.
If a reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic
countermeasures and save the remainder of the fluid for examination if deemed necessary.
Sensitivity/Resistance
Increased resistance to heparin is frequently encountered in fever, thrombosis, thrombophlebitis, infections with
thrombosing tendencies, myocardial infarction, cancer and in postsurgical patients.
Other
Excessive administration of potassium-free solutions may result in significant hypokalemia.
Solutions containing sodium ions should be used with great care in patients with congestive heart failure, severe
renal insufficiency, and in clinical states in which there exists edema with sodium retention.
In patients with diminished renal function, administration may result in sodium retention. Because dosages of the
drug are titrated to response (See Dosage and Administration).
PRECAUTIONS
Because Heparin Sodium is derived from animal tissue, it should be used with caution in patients with a history of
allergy.
Heparin Sodium and 0.9% Sodium Chloride Injection should also be used with caution in the presence of hepatic or
renal disease, hypertension, during menstruation, or in patients with indwelling catheters.
Larger doses of heparin may be necessary in the febrile state.
Solutions containing sodium should be used with caution in patients receiving corticosteroids or corticotrophin.
NO ADDITIVES SHOULD BE MADE TO HEPARIN SODIUM AND 0.9% SODIUM CHLORIDE INJECTION.
Product Monograph - Heparin Sodium and 0.9% Sodium Chloride
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Special Populations
Pregnant Women: Animal reproduction studies have not been conducted with Heparin Sodium and 0.9% Sodium
Chloride Injection. It is also not known whether Heparin Sodium and 0.9% Sodium Chloride Injection can cause
fetal harm when administered to a pregnant woman or can affect reproduction capacity. Heparin Sodium and 0.9%
Sodium Chloride Injection should be given to a pregnant woman only if clearly needed. Heparin sodium does not
cross the placental barrier.
Nursing Women: Heparin Sodium is not excreted in human milk.
Pediatrics (< 12 years of age): Safety and effectiveness in pediatric patients have not been established.
Geriatrics (> 60 years of age): A higher incidence of bleeding has been reported in patients over 60 years of age,
especially women. Clinical studies indicate that lower doses of heparin may be indicated in these patients (see
Clinical Pharmacology).
Monitoring and Laboratory Tests
Clinical evaluation and periodic laboratory determinations are necessary to monitor changes in fluid balance and
electrolyte concentration and acid base balance during prolonged parenteral therapy or whenever the condition of
the patient warrants such an evaluation.
Periodic platelet counts, hematocrits, and tests for occult blood in stool are recommended during the entire course
of heparin therapy, regardless of the route of administration.
ADVERSE REACTIONS
If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic
counter-measures, and save the remainder of the fluid for examination if deemed necessary.
Clinical Trial Adverse Drug Reactions
There are no data available on adverse reactions from Baxter-controlled clinical trials conducted with heparin
sodium.
Post-Market Adverse Drug Reactions
The following adverse reactions have been reported in the post-marketing experience and/or are known to have
been reported with the use of heparin sodium. These reactions are listed by MedDRA System Organ Class (SOC),
then by preferred term in order of severity.
BLOOD AND LYMPHATIC SYSTEM DISORDERS: Hemorrhage, Heparin-induced thrombocytopenia (HIT),
Heparin-induced thrombocytopenia and thrombosis (HITT), Heparin-associated thrombocytopenia (HAT), Delayed
HITT, Acute reversible thrombocytopenia.
IMMUNE SYSTEM DISORDERS: Anaphylactic reaction and shock, Anaphylactoid reaction and
Hypersensitivity.
ENDOCRINE SYSTEM DISORDERS: Adrenal hemorrhage (with resultant acute adrenal insufficiency),
Suppression of aldosterone synthesis.
METABOLISM AND NUTRITION DISORDERS: Rebound hyperlipemia (upon withdrawal of heparin),
Hypervolemia.
Product Monograph - Heparin Sodium and 0.9% Sodium Chloride
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NERVOUS SYSTEM DISORDERS: Headache.
VASCULAR DISORDERS: Venous thrombosis or Phlebitis, Extravasation.
GASTROINTESTINAL DISORDERS: Retroperitoneal hemorrhage, Gastrointestinal hemorrhage, Nausea and
Vomiting.
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS: Asthma, Rhinitis, Cyanosis, Tachypnea.
EYE DISORDERS: Lacrimation.
CARDIAC DISORDERS: Vasospastic reactions.
SKIN AND SUBCUTANEOUS TISSUE DISORDER: Erythema, Skin necrosis, Urticaria, Delayed Transient
Alopecia, Itching and Burning, especially on the plantar side of the feet.
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS: Osteoporosis, Arthralgia.
RENAL AND URINARY DISORDERS: Suppression of renal functions.
REPRODUCTIVE SYSTEM AND BREAST DISORDERS: Ovarian hemorrhage, Priapism.
DISORDERS AND ADMINISTRATION SITE CONDITIONS: Chest pain, Febrile response, Injection site
reactions, Chills and Fever, Sense of oppression.
INJURY, POISONING, AND PROCEDURAL COMPLICATIONS: Post procedural hematoma.
INVESTIGATIONS: Elevated blood pressure, Elevations of aminotransferase (SGOT [S-AST] and SGPT [SALT]) levels.
DRUG INTERACTIONS
Drug-Drug Interactions
Oral anticoagulants
Heparin sodium may prolong the one-stage prothrombin time. Therefore, when heparin sodium is given with
dicumarol or warfarin sodium, a period of at least 5 hours after the last intravenous dose or 24 hours after the last
subcutaneous dose should elapse before blood is drawn if a valid prothrombin time is to be obtained.
Other Interactions
Drugs such as acetylsalicylic acid, dextran, phenylbutazone, ibuprofen, indomethacin, dipyridamole,
hydroxychloroquine and others that interfere with platelet-aggregation reactions (the main hemostatic defense of
heparinized patients) may induce bleeding and should be used with caution in patients receiving heparin sodium.
Digitalis, tetracyclines, nicotine, or antihistamines may partially counteract the anticoagulant action of heparin
sodium.
Drug-Laboratory Interactions
Product Monograph - Heparin Sodium and 0.9% Sodium Chloride
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Hyperaminotransferasemia
Significant elevations of aminotransferase (SGOT [S-AST] and SGPT [S-ALT]) levels have occurred in a high
percentage of patients (and healthy subjects) who have received heparin. Since aminotransferase determinations are
important in the differential diagnosis of myocardial infarction, liver disease, and pulmonary emboli, rises that
might be caused by drugs (like heparin) should be interpreted with caution.
DOSAGE AND ADMINISTRATION
Dosing Considerations
Heparin Sodium is not effective by oral administration and Heparin Sodium and 0.9% Sodium Chloride Injection
should not be given orally.
Recommended Dose and Dosage Adjustment
Heparin administration procedures vary and are adjusted to the requirements of the individual patient by the
attending physician, but a proper heparinization schedule MUST BE initiated before and maintained throughout
dialysis to prevent clotting and subsequent blood path obstruction.
Dosage is dependent upon the age, weight and clinical conditions of the patient, in addition to the procedure being
employed.
Administration
Priming fluid should contain 2000 USP heparin units per 1000 mL of 0.9% Sodium Chloride Injection.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration
whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral
solutions, where possible.
Because dosages of this drug are titrated to response, no additives should be made to Heparin Sodium and 0.9%
Sodium Chloride Injection.
It is recommended that the intravenous administration apparatus be replaced at least every 24 hours.
All injections in VIAFLEX Plus plastic containers are intended for administration using sterile equipment.
Note: Read dialyzer direction sheets and follow manufacturer’s directions for use.
DIRECTION FOR USE OF VIAFLEX PLUS PLASTIC CONTAINER
Warning: Do not use plastic containers in series connections. Such use could result in air embolism due to residual
air being drawn from the primary container before administration of the fluid from the secondary container is
completed.
To Open
Tear overwrap down side at slit and remove solution container. Do not remove unit from overwrap until ready for
use. The overwrap is a moisture barrier. The inner bag maintains the sterility of the product. After removing
overwrap, check for minute leaks by squeezing inner bag firmly. If leaks are found discard solution as sterility may
be impaired. Do not add supplementary medication.
Preparation for Administration
Product Monograph - Heparin Sodium and 0.9% Sodium Chloride
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1. Suspend container from eyelet support.
2. Remove plastic protector from outlet port at bottom of container.
3. Attach administration set. Refer to complete directions accompanying set.
OVERDOSAGE
For management of a suspected drug overdose, contact your regional Poison Control Centre.
Symptoms
Bleeding is the primary sign of heparin sodium overdosage. Nosebleeds, blood in urine or tarry stools may be noted
as the first sign of bleeding. Easy bruising or petechial formations may precede frank bleeding.
Treatment
Neutralization of heparin effect.
If reversal of heparinization is desired or in the case of overdosage, protamine sulfate (1% solution) by slow
infusion is utilized. No more than 50 mg should be given very slowly in a 10 minute period. Each mg of protamine
sulfate neutralizes approximately 100 units of heparin sodium (or 1.0 to 1.5 mg neutralizes approximately 1.0 mg of
heparin). Heparins derived from various animal sources require different amounts of protamine sulfate for
neutralization. This fact is of most importance during procedures of regional heparinization, including dialysis.
Decreasing amounts of protamine are required as time from the last heparin injection increases. For example, thirty
minutes after a dose of heparin, approximately 0.5 mg of protamine is sufficient to neutralize each 100 USP units of
heparin. Blood or plasma transfusions may be necessary; these dilute but do not neutralize heparin.
ACTION AND CLINICAL PHARMACOLOGY
Mechanism of Action
Heparin sodium inhibits reactions which lead to the clotting of blood and the formation of fibrin clots both in vitro
and in vivo. Heparin sodium acts at multiple sites in the normal coagulation system. Small amounts of heparin
sodium in combination with antithrombin III (heparin co-factor) can prevent the development of a hypercoagulable
state by inactivating activated Factor X, preventing the conversion of prothrombin to thrombin. Once a
hypercoagulable state exists, larger amounts of heparin sodium in combination with antithrombin III can inhibit the
coagulation process by inactivating thrombin and earlier clotting intermediates, thus preventing the conversion of
fibrinogen to fibrin. Heparin sodium also prevents the formation of a stable fibrin clot by inhibiting the activation
of the fibrin stabilizing factor.
Bleeding time is usually unaffected by heparin sodium. Clotting time is prolonged by full therapeutic doses of
heparin sodium; in most cases it is not measurably affected by low doses of heparin sodium. Heparin sodium does
not have fibrinolytic activity; therefore it will not lyse existing clots.
Patients over 60 years of age, following similar doses of heparin, may have higher plasma levels of heparin and
longer activated partial thromboplastin times (APTTs) compared with patients under 60 years of age.
Pharmacokinetics
Peak plasma levels of heparin sodium are achieved 2 to 4 hours following subcutaneous administration, although
there are considerable individual variations. Loglinear plots of heparin sodium plasma concentrations with time, for
a wide range of dose levels, are linear, which suggests the absence of zero order processes. The liver and the
reticulo-endothelial system are the sites of biotransformation. The biphasic elimination curve, a rapidly declining
Product Monograph - Heparin Sodium and 0.9% Sodium Chloride
Page 10 of 17
alpha phase (t 1/2 = 10 min.), and after the age of 40 a slower beta phase, indicates uptake in organs. The absence of
a relationship between anticoagulant half-life and concentration half-life may reflect factors such as protein binding
of heparin sodium.
The plasma half-life is approximately 1½ hours, however the half-life increases with increasing doses ranging from
approximately 1 hour with a dose of 100 units/kg to approximately 2½ hours with a dose of 400 units/kg.
Special Populations and Conditions
The plasma half-life may be prolonged in patients with cirrhosis or severe renal impairment. Patients with
pulmonary embolism may have a more rapid clearance of heparin sodium. Heparin sodium is not removed by
hemodialysis.
STORAGE AND STABILITY
Protect from freezing.
Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. It is recommended the
product be stored at room temperature (15-25°C); brief exposure up to 40°C does not adversely affect the product.
SPECIAL HANDLING INSTRUCTIONS
See STORAGE AND STABILITY.
DOSAGE FORMS, COMPOSITION AND PACKAGING
Heparin Sodium and 0.9% Sodium Chloride Injection is a sterile nonpyrogenic solution of Heparin Sodium, USP
derived from porcine intestinal mucosa, standardized for use as an anticoagulant, in 0.9% Sodium Chloride (NaCl)
Injection.
Each 100 mL of Heparin Sodium in 0.9% Sodium Chloride Injection contains:
Drug Substance
Heparin Sodium, USP
Sodium Chloride
200 Units
900 mg
Excipients
Citric Acid, USP (Buffers)
Dibasic Sodium Phosphate, USP (Buffers)
Water for Injection, USP
36.2mg
228.0 mg
qs
Osmolarity (actual):
The pH of the solution is approximately 7.0.
358 mOsmol/L.
The approximate ionic concentrations are as follows:
Approx. mmol/L
Sodium
Chloride
186.4
154
Product Monograph - Heparin Sodium and 0.9% Sodium Chloride
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Phosphate (as HPO 4 2-)
Citrate
Approx. mEq/L
Sodium
Chloride
Phosphate (as HPO 4 2-)
Citrate
16.2
1.9
186.4
154
32.4
1.9
The VIAFLEX PLUS plastic container is fabricated from a specially formulated polyvinyl chloride (PL 146
plastic). Water can permeate from inside the container into the overwrap in amounts insufficient to affect the
solution significantly. Solutions in contact with the plastic container can leach out certain of its chemical
components in very small amounts within the expiration period, e.g., di-2-ethylhexylphthalate (DEHP), up to 5
parts per million. However, the safety of the plastic has been confirmed in tests in animals according to USP
biological tests for plastic containers as well as by tissue culture toxicity studies.
Heparin Sodium in 0.9% Sodium Chloride Injection is supplied in VIAFLEX PLUS plastic (polyvinyl chloride)
containers in the following sizes and concentrations:
•
•
500 mL 1000 USP Heparin Units in 0.9% Sodium Chloride
1000 mL 2000 USP Heparin Units in 0.9% Sodium Chloride
Product Monograph - Heparin Sodium and 0.9% Sodium Chloride
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PART II: SCIENTIFIC INFORMATION
PHARMACEUTICAL INFORMATION
Drug Substance – Heparin Sodium
Proper name: Heparin sodium, USP
Chemical name: Heparin sodium
Structural formula:
Heparin is a heterogeneous group of straight-chain anionic mucopolysaccharides, called glycosaminoglycans,
having anticoagulant properties. Although others may be present, the main sugars occurring in heparin are (1) α-Liduronic acid-2-sulfate, (2) 2-deoxy-2-sulfamino-α-D-glucose 6-sulfate, (3) ß-D-glucuronic acid, (4) 2-acetamido-2deoxy-α-D-glucose, and (5) α-L-iduronic acid. These sugars are present in decreasing amounts, usually in the order
(2)>(1)>(4)>(3)>(5), and are joined by glycosidic linkages, forming polymers of varying sizes. Heparin is strongly
acidic because of its content of covalently linked sulfate and carboxylic acid groups. In heparin sodium, the acidic
protons of the sulfate units are partially replaced by sodium ions.
Drug Substance –Sodium Chloride
Proper name: Sodium Chloride
Chemical name: Sodium Chloride
Molecular formula and molecular mass: NaCl, 58.54g/mol
Physicochemical properties: Soluble in water, glycerol. Very slightly soluble in alcohol
Product description
Heparin Sodium and 0.9% Sodium Chloride Injection is a sterile nonpyrogenic solution of Heparin Sodium, USP
derived from porcine intestinal mucosa, standardized for use as an anticoagulant. The anticoagulant potency of the
heparin sodium is determined by a biological assay using a USP reference.
TOXICOLOGY
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Studies on the carcinogenic potential, reproductive and developmental toxicity, and genotoxic potential of the
components of Heparin Sodium and 0.9% Sodium Chloride Injection have not been performed.
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IMPORTANT: PLEASE READ
PART III: CONSUMER INFORMATION
HEPARIN SODIUM IN 0.9% SODIUM
CHLORIDE INJECTION
Heparin Sodium, USP and Sodium Chloride, USP
This leaflet is part III of a three-part "Product
Monograph" is designed specifically for Consumers.
This leaflet is a summary and will not tell you
everything about HEPARIN SODIUM IN 0.9%
SODIUM CHLORIDE INJECTION. Contact your
doctor or pharmacist if you have any questions
about the drug.
ABOUT THIS MEDICATION
What the medication is used for:
This medication belongs to a group of medicines
known as anticoagulants. Heparin Sodium in 0.9%
Sodium Chloride Injection is used as anticoagulant in
extracorporeal circulation and dialysis procedure. It is
also used as an aid in maintenance of catheter patency.
What it does:
This medication works by decreasing the clotting
ability of your blood and helping stop clots from
forming in the blood vessels.
When it should not be used:
Do not use this medication if you have had or currently
have any of the following:
• A known allergy to heparin, pork, or sulfites;
• a severe decrease in the number of platelets in
the blood
• uncontrollable bleeding
What the medicinal ingredient is:
Heparin Sodium, USP
Sodium Chloride, USP
1 of the product monograph.
What dosage forms it comes in:
This medication is a sterile solution for intravenous
administration that comes in the following dosages:
1000 USP Heparin Units in 500mL 0.9% Sodium
Chloride Injection
2000 USP Heparin Units in 1000mL 0.9% Sodium
Chloride Injection
WARNINGS AND PRECAUTIONS
BEFORE you use HEPARIN SODIUM IN 0.9%
SODIUM CHLORIDE INJECTION talk to your
doctor, pharmacist or nurse if:
• you are having an epidural or spinal anaesthetic. It
is important that you remind your doctor that you are
receiving heparin infusion before you receive any
anaesthetic
• you have or have had in the past, injury or surgery on
the brain, spinal cord, or eyes
• you have any condition which makes you likely to
bleed more easily, regardless of the reason. Ask
your doctor if unsure.
• you are menstruating.
• you often consume alcohol.
• you suffer from kidney or liver problems.
• you are pregnant or nursing, or may become
pregnant.
• you are over 60 years of age.
• you have a severe decrease in the number of platelets
in the blood
• you have bacterial infection inside of the heart
(bacterial endocarditis)
• you have high blood pressure (hypertension)
• you have ulcerative lesions of the small intestine or
stomach
INTERACTIONS WITH THIS MEDICATION
What the important nonmedicinal ingredients are:
Citric Acid,Anhydrous, USP
Dibasic Sodium Phosphate, USP
Tell your doctor if you are taking or have recently
taken any medications, including medications that do
not require a prescription.
For a full listing of nonmedicinal ingredients see Part
Tell your doctor, pharmacist or nurse if you are taking
any of the following medicines:
Product Monograph - Heparin Sodium and 0.9% Sodium Chloride
Page 15 of 17
Drugs that affect blood clotting (e.g. anticoagulants,
antithrombotic drugs, platelet inhibitors, and
thrombolytics). You may be likely to bleed more
easily.
Non-steroidal anti-inflammatory drugs (e.g. ibuprofen)
for arthritis or pain. You may be likely to bleed more
easily
Salicylates (such as aspirin) for reducing pain and
inflammation, or for stopping harmful blood clots from
forming. You may be likely to bleed more easily
Digitalis, tetracyclines, nicotine, and antihistamines.
These medications may partially counteract the
anticoagulant activity of heparin sodium.
PROPER USE OF THIS MEDICATION
Usual dose:
Your doctor will determine your dosage according to
the results of suitable laboratory tests.
The rate for infusion of the medication is dependent
upon age, weight, clinical condition of the patient and
the procedure being employed.
Administration:
Heparin is not intended for intramuscular use.
Your doctor should not use Heparin Sodium in 0.9%
Sodium Chloride Injection for catheter lock flush
procedure.
Overdose:
Bleeding is the primary sign of heparin sodium
overdosage. Nosebleeds, blood in urine, tarry stools or
easy bruising may be noted as the first sign of bleeding.
In case of drug overdose, contact a health care
practitioner, hospital emergency department or
regional Poison Control Centre immediately, even if
there are no symptoms. Your doctor may treat you
with protamine sulphate to neutralize the heparin
sodium.
SIDE EFFECTS AND WHAT TO DO ABOUT
THEM
This medication may cause side effects. Do not be
alarmed by this list of side effects, you may not
experience any of them. However, tell your doctor or
nurse if you do not feel well while you are being given
heparin sodium. Ask your doctor or nurse to answer
any questions that you may have.
Tell your doctor or nurse immediately if you
experience any of the following as these side effects
may be serious and you may need urgent medical
attention:
• If you experience any of the following after
having an epidural or spinal anaesthetic:
tingling, weakness or numbness in your legs or
lower body, back pain, loss of control of your
bowel or bladder.
• Signs of stroke (bleeding in the brain), such as:
severe headache, severe nausea and vomiting,
dizziness, confusion.
• Signs of bleeding in the abdomen, such as:
abdominal or stomach pain, back pain, blood in
urine or stool, vomiting of blood, black stool
(tarry stool).
• Signs of an allergic reaction to this medication ,
such as: rash, itching, hives on the skin,
swelling of the face, lips, tongue or other parts
of the body, shortness of breath, wheezing,
trouble breathing.
• Chest pain, rapid or unusual heart beat,
• Bleeding episodes such as unexplained
nosebleeds, heavy menstrual periods, bleeding
from gums while brushing teeth, bleeding or
oozing from surgical wounds.
• Spontaneous bruising (bruise not caused by
injury)
• Unexplained skin lesions (sores)
• Pain or swelling of legs or feet
• Discoloration (purple or red) and pain around
the injection site
• Prolonged, painful erection
• Fever
• Chills
This is not a complete list of side effects. For any
unexpected effects while taking HEPARIN SODIUM
Product Monograph - Heparin Sodium and 0.9% Sodium Chloride
Page 16 of 17
IN 0.9% SODIUM CHLORIDE INJECTION, contact
your doctor or pharmacist.
HOW TO STORE IT
Store at room temperature (15 to 250C). Protect from
freezing. Excessive heat should be avoided.
This leaflet was prepared by Baxter Corporation,
Mississauga, ON L5N 0C2.
Last revised: July 05, 2013
REPORTING SUSPECTED SIDE EFFECTS
You can report any suspected adverse reactions
associated with the use of health products to the
Canada Vigilance Program by one of the
following 3 ways:
------------------------------------------------------------------------• Report online at
www.healthcanada.gc.ca/medeffect
• Call toll-free at 1-866-234-2345
• Complete a Canada Vigilance Reporting
Form and:
- Fax toll-free to 1-866-678-6789, or
- Mail to:
Canada
Vigilance Program
Health Canada
Postal Locator 0701D
Ottawa, Ontario
K1A 0K9
Postage paid labels, Canada Vigilance
Reporting Form and the adverse reaction
reporting guidelines are available on the
MedEffect™ Canada Web site at
www.healthcanada.gc.ca/medeffect.
NOTE: Should you require information related to
the management of side effects, contact your health
professional. The Canada Vigilance Program does
not provide medical advice.
MORE INFORMATION
This document plus the full product monograph,
prepared for health professionals can be found at:
http://www.baxter.ca.
or by contacting the sponsor, Baxter Corporation, at:
1-800-387-83-99
Product Monograph - Heparin Sodium and 0.9% Sodium Chloride
Page 17 of 17